Evaluation du devenir des néphropathies sévères chez l'enfant traitées par bolus de méthylprédnisolone (étude rétrospective de 1986 a 2010)

Contexte: Les néphropathies sévères du purpura rhumatoïde (NSPR) sont rares mais peuvent se compliquer d insuffisance rénale terminale dans plus de 20% des cas en l absence de traitement. Les protocoles thérapeutiques sont controversés et il n existe pas de prise en charge uniforme. Objectif: Les objectifs de cette étude étaient d estimer la prévalence de l insuffisance rénale terminale et de la rémission à un an et à long terme de notre cohorte de patients traités par bolus de méthylprednisolone (MP), de classifier leur évolution globale et d évaluer les effets secondaires du traitement, notamment sur la croissance staturo-pondérale. Méthodes: Il s agissait d une étude rétrospective menée dans le Nord-Pas de Calais entre 1986 et 2010, chez des enfants atteints d une NSPR. L atteinte sévère était définie par un ratio protéinurie/créatininurie (P/C) > 1 g/g, ou par une protéinurie > 20 mg/kg/j ou > 1 g/l. Les patients étaient traités par 3 bolus de MP (1g/1,73m2 chacun), suivis d une corticothérapie orale (30 mg/m2/j durant un mois, puis décroissance progressive). Le cyclophosphamide, la ciclopsorine et/ou des anti-protéinuriques étaient associés en cas de protéinurie persistante. La rémission était définie comme un ratio P/C < 0,2. Résultats: 70 enfants (âge moyen: 8 ans) atteints de NSPR ont été traités par bolus de méthylprednisolone entre 1986 et 2010. L atteinte initiale était caractérisée par une protéinurie modérée pour 27 % d entre eux, une protéinurie néphrotique pour 32 %, un syndrome néphrotique pour 40 % et une insuffisance rénale aiguë pour 1 %. Le protocole thérapeutique était appliqué correctement chez 71 % des patients. Les corticoïdes étaient prescrits seuls dans 71 % des cas. Le cyclophosphamide était associé dans 19 % des cas, la ciclosporine dans 4 % et les anti-protéinuriques dans 20 %. Aucun effet secondaire grave n était rapporté. Une prise de poids significative était mise en évidence au cours du suivi, sans différence significative sur la taille. Aucun patient n était en insuffisance rénale terminale à un an. Une patiente, non observante, était en insuffisance rénale terminale après 3 ans de prise en charge. 73 % des patients étaient en rémission à un an et 80 % après un suivi moyen de 5 ans (extrêmes: 1-21 ans). Conclusion: Les bolus de méthylprednisolone sont efficaces et sûrs pour le traitement des NSPR et doivent être considérés comme la première option thérapeutique.LILLE2-BU Santé-Recherche (593502101) / SudocSudocFranceF

ARTERIAL HYPERTENSION IS PREVALENT IN PEDIATRIC HEMODIALYSIS AND RELATED TO DIALYSATE SODIUM CONCENTRATION AND WEEKLY DIALYSIS TIME -DATA FROM THE INTERNATIONAL PEDIATRIC HEMODIALYSIS NETWORK (IPHN)

WOS: 00044399840002

Haemodiafiltration does not lower protein-bound uraemic toxin levels compared with haemodialysis in a paediatric population

Background Haemodiafiltration (HDF) is accepted to effectively lower plasma levels of middle molecules in the long term, while data are conflicting with respect to the additive effect of convection on lowering protein-bound uraemic toxins (PBUTs). Here we compared pre-dialysis β2-microglobulin (β2M) and PBUT levels and the percentage of protein binding (%PB) in children on post-dilution HDF versus conventional high- (hf) or low-flux (lf) haemodialysis (HD) over 12 months of treatment. Methods In a prospective multicentre, non-randomized parallel-arm intervention study, pre-dialysis levels of six PBUTs and β2M were measured in children (5–20 years) on post-HDF (n = 37), hf-HD (n = 42) and lf-HD (n = 18) at baseline and after 12 months. Analysis of variance was used to compare levels and %PB in post-HDF versus conventional hf-HD and lf-HD cross-sectionally at 12 months and longitudinal from baseline to 12 months. Results For none of the PBUTs, no difference was found in either total and free plasma levels or %PB between post-HDF versus the hf-HD and lf-HD groups. Children treated with post-HDF had lower pre-dialysis β2M levels [median 23.2 (21.5; 26.6) mg/dL] after 12 months versus children on hf-HD [P<0.01; 35.2 (29.3; 41.2) mg/dL] and children on lf-HD [P<0.001; 47.2 (34.3; 53.0) mg/dL]. While β2M levels remained steady in the hf-HD and lf-HD group, a decrease in β2M was demonstrated for children on post-HDF (P<0.01). Conclusions While post-HDF successfully decreased β2M, no additive effect on PBUT over 12 months of treatment was found. PBUT removal is complex and hampered by several factors. In children, these factors might be different from adults and should be explored in future research

DNASE1L3 deficiency, new phenotypes, and evidence for a transient type I IFN signaling

peer reviewedBACKGROUND: Deoxyribonuclease 1 like 3 (DNASE1L3) is a secreted enzyme that has been shown to digest the extracellular chromatin derived from apoptotic bodies, and DNASE1L3 pathogenic variants have been associated with a lupus phenotype. It is unclear whether interferon signaling is sustained in DNASE1L3 deficiency in humans. OBJECTIVES: To explore interferon signaling in DNASE1L3 deficient patients. To depict the characteristic features of DNASE1L3 deficiencies in human. METHODS: We identified, characterized, and analyzed five new patients carrying biallelic DNASE1L3 variations. Whole or targeted exome and/or Sanger sequencing was performed to detect pathogenic variations in five juvenile systemic erythematosus lupus (jSLE) patients. We measured interferon-stimulated gene (ISG) expression in all patients. We performed a systematic review of all published cases available from its first description in 2011 to March 24(th) 2022. RESULTS: We identified five new patients carrying biallelic DNASE1L3 pathogenic variations, including three previously unreported mutations. Contrary to canonical type I interferonopathies, we noticed a transient increase of ISGs in blood, which returned to normal with disease remission. Disease in one patient was characterized by lupus nephritis and skin lesions, while four others exhibited hypocomplementemic urticarial vasculitis syndrome. The fourth patient presented also with early-onset inflammatory bowel disease. Reviewing previous reports, we identified 35 additional patients with DNASE1L3 deficiency which was associated with a significant risk of lupus nephritis and a poor outcome together with the presence of anti-neutrophil cytoplasmic antibodies (ANCA). Lung lesions were reported in 6/35 patients. CONCLUSIONS: DNASE1L3 deficiencies are associated with a broad phenotype including frequently lupus nephritis and hypocomplementemic urticarial vasculitis with positive ANCA and rarely, alveolar hemorrhages and inflammatory bowel disease. This report shows that interferon production is transient contrary to anomalies of intracellular DNA sensing and signaling observed in Aicardi-Goutières syndrome or STING-associated vasculitis in infancy (SAVI)

Mortality in Children Treated With Maintenance Peritoneal Dialysis: Findings From the International Pediatric Peritoneal Dialysis Network Registry

Rationale & Objective: Research on pediatric kidney replacement therapy (KRT) has primarily focused on Europe and North America. In this study, we describe the mortality risk of children treated with maintenance peritoneal dialysis (MPD) in different parts of the world and characterize the associated demographic and macroeconomic factors. Study Design: Prospective cohort study. Setting & Participants: Patients younger than 19 years at inclusion into the International Pediatric Peritoneal Dialysis Network registry, who initiated MPD between 1996 and 2017. Exposure: Region as primary exposure (Asia, Western Europe, Eastern Europe, Latin America, North America, and Oceania). Other demographic, clinical, and macroeconomic (4 income groups based on gross national income) factors also were studied. Outcome: All-cause MPD mortality. Analytical Approach: Patients were observed for 3 years, and the mortality rates in different regions and income groups were calculated. Cause-specific hazards models with random effects were fit to calculate the proportional change in variance for factors that could explain variation in mortality rates. Results: A total of 2,956 patients with a median age of 7.8 years at the start of KRT were included. After 3 years, the overall probability of death was 5%, ranging from 2% in North America to 9% in Eastern Europe. Mortality rates were higher in low-income countries than in high-income countries. Income category explained 50.1% of the variance in mortality risk between regions. Other explanatory factors included peritoneal dialysis modality at start (22.5%) and body mass index (11.1%). Limitations: The interpretation of interregional survival differences as found in this study may be hampered by selection bias. Conclusions: This study shows that the overall 3-year patient survival on pediatric MPD is high, and that country income is associated with patient survival